The use of nanotechnology in cancer is emerging globally. Although there are few reports on nanoparticles in cancer therapy but all have various drawbacks such as toxicity, low release kinetics of drug, low circulation stability and so on.
Lipidic nanoparticles (e.g. Doxil, a pegylated liposomal formulation of doxorubicin hydrochloride) and albumin-complexes (e.g. Abraxane, a paclitaxel-albumin complex) nanoparticles are used in humans and have been demonstrated as having improved systemic toxicity profile and have helped resolve certain formulation challenges (Ferrari M, Nature Rev. Cancer, 2005, 5:161). Platinum-based chemotherapeutic agents are used as first line of therapy in over 70% of all cancers. Cisplatin undergoes rapid formation of cis-[Pt(NH3)2Cl(OH2)]+ and cis-[Pt(NH3)2(OH2)]2+ resulting in nephrotoxicity. Further, aquation of both carboplatin and oxaliplatin are significantly slower, resulting in decreased potency. In the recent past, considerable progress has been made wherein, Dhar et al (PNAS, 2008, 105, 17356) generated a platinum (IV) complex (c,t,c-[Pt(NH3)2(O2CCH2CH2CH2CH2CH3)2Cl2] that is hydrophobic enough for encapsulation into PLGA-b-PEG nanoparticles. However, the prodrug in this case has to be intracellularly processed into cisplatin. Furthermore, alternative strategies based on conjugation of platinum to polymers (e.g. a polyamidoamine dendrimer-platinum complex) resulted in a 200-550 fold reduction in cytotoxicity than free cisplatin. This was a result of strong bonds formed between the polymer and platinum (J Pharm Sci, 2009, 98, 2299). Another example is AP5280, a N-(2-hydroxypropyl) methacrylamide copolymer-bound platinum that is less potent than carboplatin. Here, the platinum is held by an aminomalonic acid chelating agent coupled to the COOH-terminal glycine of a tetrapeptide spacer (Clin Can Res, 2004, 10, 3386; Eur J Can, 2004, 40, 291).
Further, WO 2010/091192 A2 (Sengupta et al) discloses biocompatible conjugated polymer nanoparticles including a copolymer backbone, a plurality of sidechains covalently linked to said backbone, and a plurality of platinum compounds dissociably linked to said backbone. The disclosure is further directed to dicarbonyl-lipid compounds wherein a platinum compound is dissociably linked to the dicarbonyl compound.
However, various drawbacks are associated with the presently employed nanoparticles. The present disclosure aims at overcoming the drawbacks of the prior art and providing for stable, potent and safer nano-platinates in cancer chemotherapy.